Authors' objectives: Newborn bloodspot screening offers the potential to detect rare diseases early, enabling timely treatment that can reduce mortality and morbidity. Generating evidence for rare diseases often depends on observational data, making it challenging to formulate recommendations for new screening programmes and evaluate the effectiveness of existing ones. To identify the range of methods and mechanisms used to measure and monitor outcomes from newborn screening programmes using a scoping review.

Authors' results and conclusions: We included 574 primary studies and extracted data from 178. Of the 75 studies in group 1, most compared screen-detected cases with controls (74%). Studies in this group used newborn bloodspot programme databases, registries or record review to identify participants and outcomes; only six (8%) reported use of record linkage. Studies in group 2 (n = 31) mostly reported comparisons of screening tests (25, 81%). Over half of studies in group 3 (n = 34) used newborn bloodspot programme databases to identify participants (53%) and outcomes (65%). A similar pattern was seen in the group 4 (n = 38). Studies reporting follow-up typically relied on retrospective record review or were not well reported. Across all study groups, data on accuracy, epidemiology and genetic variants were common. Studies in group 1 also reported on the effectiveness of newborn bloodspot screening (32/75, 43%), treatment effectiveness (20%) or harms of newborn bloodspot screening (3%). Many studies reported test accuracy metrics and genetic variants in newborn screening. Some data on programme effectiveness were identified, but assessment of potential harms remains limited, and methods for follow-up were poorly reported. Assessment of harms, including overdiagnosis and psychological impact, is crucial to ensuring a net benefit at the population level.

Authors' methods: We included studies published between 2019 and 2024, which evaluated a current or candidate newborn screening programme, or which reported outcomes in screen-detected cases. Studies were categorised into four groups: group 1 reported a comparison and follow-up; group 2 reported a comparison but no follow-up; group 3 reported no comparison with follow-up; and group 4 reported no comparison or follow-up. Data were extracted from a random sample of studies within each group; studies in group 1 were prioritised. Results were reported narratively according to study group. The review was conducted and reported according to current guidance for scoping reviews. EMBASE (Ovid), MEDLINE (Ovid) and Science Citation Index (Web of Science – Clarivate). Restricting data extraction to a random sample of studies risks missing novel methods or mechanisms.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/NIHR167910

Year Published: 2026

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/published-articles/GJJD1717

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/GJJD1717

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk